% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Wang:296086,
author = {J. Wang and L. Liao and B. Miao$^*$ and B. Yang and B. Li
and X. Ma and A. Fitz$^*$ and S. Wu and J. He and Q. Zhang
and S. Ji and G. Jin and J. Zhang and Y. Cao and H. Wang and
W. Qin and C. Sun$^*$ and R. Bernards and C. Wang},
title = {{D}eciphering the role of the {MALT}1-{RC}3{H}1 axis in
regulating {GPX}4 protein stability.},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {122},
number = {1},
issn = {0027-8424},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {DKFZ-2025-00034},
pages = {e2419625121},
year = {2025},
note = {#EA:D250#},
abstract = {Ferroptosis, a unique form of iron-dependent cell death
triggered by lipid peroxidation accumulation, holds great
promise for cancer therapy. Despite the crucial role of GPX4
in regulating ferroptosis, our understanding of GPX4 protein
regulation remains limited. Through FACS-based genome-wide
CRISPR screening, we identified MALT1 as a regulator of GPX4
protein. Inhibition of MALT1 expression enhances GPX4
ubiquitination-mediated degradation by up-regulating the E3
ubiquitin ligase RC3H1. Using both rescue assays and
functional genetic screening, we demonstrate that
pharmacologically targeting MALT1 triggers ferroptosis in
liver cancer cells. Moreover, we show that targeting MALT1
synergizes with sorafenib or regorafenib to induce
ferroptosis across multiple cancer types. These findings
elucidate the modulatory effects of the MALT1-RC3H1 axis on
GPX4 stability, revealing a molecular mechanism that could
be exploited to induce ferroptosis for cancer therapy.},
keywords = {Humans / Phospholipid Hydroperoxide Glutathione Peroxidase:
metabolism / Phospholipid Hydroperoxide Glutathione
Peroxidase: genetics / Ferroptosis: genetics /
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1
Protein: metabolism / Mucosa-Associated Lymphoid Tissue
Lymphoma Translocation 1 Protein: genetics / Protein
Stability / Ubiquitin-Protein Ligases: metabolism /
Ubiquitin-Protein Ligases: genetics / Sorafenib:
pharmacology / Cell Line, Tumor / Ubiquitination / Liver
Neoplasms: metabolism / Liver Neoplasms: genetics / Liver
Neoplasms: drug therapy / Liver Neoplasms: pathology /
Phenylurea Compounds: pharmacology / Gene Expression
Regulation, Neoplastic / Pyridines / GPX4 (Other) / MALT1
(Other) / ferroptosis (Other) / liver cancer (Other) /
Phospholipid Hydroperoxide Glutathione Peroxidase (NLM
Chemicals) / Mucosa-Associated Lymphoid Tissue Lymphoma
Translocation 1 Protein (NLM Chemicals) / Ubiquitin-Protein
Ligases (NLM Chemicals) / MALT1 protein, human (NLM
Chemicals) / Sorafenib (NLM Chemicals) / regorafenib (NLM
Chemicals) / Phenylurea Compounds (NLM Chemicals) /
Pyridines (NLM Chemicals)},
cin = {D250},
ddc = {500},
cid = {I:(DE-He78)D250-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39739814},
doi = {10.1073/pnas.2419625121},
url = {https://inrepo02.dkfz.de/record/296086},
}